Full Press Release Details
AVROBIO Announces New Positive Clinical Data and Preclinical Data,
as Well as Expanded Leading Lysosomal Disorder Gene Therapy Pipeline
Three months post-gene therapy, first patient in Gaucher trial shows reductions in the toxic metabolite
plasma lyso-Gb1 and plasma chitotriosidase as compared to baseline when the patient was on ERT
Ongoing Fabry disease trials continue to demonstrate sustained durability,
with first patient out 3.5 years
One year post-gene therapy, first patient in cystinosis trial remains off cysteamine, with positive
data across multiple measures, including substantial reduction in cystine crystals in cornea
Clinical trial recruitment gaining momentum with five new patients expected to be dosed,
enrolled or consented in 4Q 2020
Gaucher disease type 3 program added to pipeline; recently added Hunter syndrome
program planned to enter clinic next year
Virtual R&D Day to be webcast today starting at 9 a.m. ET
CAMBRIDGE, Mass., Nov. 17, 2020 AVROBIO, Inc. (Nasdaq: AVRO), a leading clinical-stage gene therapy company with a mission to free people from a
lifetime of genetic disease, today announced positive new data across its clinical programs in Gaucher disease type 1, Fabry disease and cystinosis, further reinforcing the potential of ex vivo lentiviral gene therapy for lysosomal disorders.
Additionally, AVROBIO is further expanding its lysosomal disorder pipeline with a new program in Gaucher disease type 3, which joins the recently announced program in Hunter syndrome in a synergistic portfolio of six programs designed to prevent,
halt or reverse genetic disease.
We re delighted to report substantial new data across our three clinical programs. Three months post-gene
therapy infusion, the first Gaucher disease patient s levels of the toxic metabolite plasma lyso-Gb1, as well as plasma chitotriosidase, were lower than the baseline levels when the patient was still on
enzyme replacement therapy (ERT). With our Fabry disease data continuing to reflect sustained and durable results, with our first patient now out 3.5 years from dosing, we are planning our strategy to seek accelerated approvals in one or more major
markets, said Geoff MacKay, president and CEO of AVROBIO. Additionally, the first patient in the investigator-sponsored trial for cystinosis, now out one year, remains off both oral and eye drop cysteamine and we are thrilled to announce
that a third patient has been dosed.
As we move into the next stage of company growth, we re expanding our lysosomal disorder pipeline
with a new program for Gaucher disease type 3 and we plan to dose the first Hunter syndrome patient next year. We expect to be the first lentiviral gene therapy to the clinic across all six of these indications and in some cases, the first to
be in the clinic with an investigational gene therapy of any type. We believe the new data we ve announced today help de-risk our portfolio which leverages the same lentiviral gene therapy approach across
indications, MacKay added. With strong clinical trial enrollment momentum coming out of the COVID-19-related slowdown, we anticipate dosing, enrolling or
consenting five patients across our clinical trials this quarter, and dosing a total of 30 patients cumulatively across our clinical programs by the end of 2021.
Positive clinical data out as far as 3.5 years across a broad lysosomal disorder gene therapy pipeline
New clinical updates announced today include:
Three months post-gene therapy, the first patient dosed had a
22-percent reduction in the toxic metabolite plasma lyso-Gb1, a sensitive and clinically validated biomarker for Gaucher disease, compared to a baseline taken when she
was stable on ERT, the current standard of care. Additionally, she had a 17-percent drop from her ERT baseline in plasma chitotriosidase, a biomarker of activated macrophages or Gaucher cells which
lead to inflammation and severe organ damage. The vector copy number (VCN) at three months was 0.6 vcn/dg. Additionally, hemoglobin concentration and platelet counts, which are typically low in Gaucher disease patients, remained in the normal range
three months after gene therapy. Patient 1 discontinued ERT one month before the gene therapy infusion and remains off ERT.
months post-gene therapy, no unexpected safety events or trends have been identified in the trial, with no serious adverse events related to AVR-RD-02 reported in the
first patient dosed as of the safety data cut-off date, Nov. 3, 2020.
With data from both trials showing consistently favorable results up to 3.5 years post-gene therapy, AVROBIO is in advanced planning of its
strategy toward potential accelerated approval pathways. The company intends to submit its briefing book in 4Q 2020 to the U.S. Food and Drug Administration (FDA) with the goal to align on a potential accelerated approval strategy.
The company reported durable and sustained response in enzyme activity, substrate levels and VCN across patients in both the Phase 1 and Phase
2 trials as of the data cut-off date, indicating successful engraftment of genetically modified cells and endogenous production of the functional enzyme needed to break down toxic substrate and metabolites in
patients. Updated biomarker data on kidney function show generally stable estimated glomerular filtration rate (eGFR) in both Phase 1 and Phase 2 patients. Historically, people living with Fabry disease experience a progressive, faster-than-normal
rate of decline in kidney function, as measured by eGFR, whether or not they are on ERT, the current standard of care. AVROBIO believes the stability in eGFR for patients in its clinical trials to be clinically significant and relevant.
No unexpected safety events or trends have been identified in the trials as of the safety data cut-off
date, Oct. 8, 2020. The eight serious adverse events reported in the two Fabry disease trials have been consistent with the conditioning regimen, stem cell mobilization, underlying disease or pre-existing
conditions. Pre-existing low anti-AGA antibody titers have been detected in four patients in the Fabry Phase 1 trial and a transient low titer was observed but not
detectable in subsequent measures in one patient in the Fabry Phase 2 trial.
patient dosed in the Phase 1/2 trial, now 12 months post-dosing, remains off both oral and eye drop cysteamine. Biopsy data showed a 56-percent decrease in the number of crystals in his skin, suggesting that
the patient may now be producing his own functional cystinosin protein which he was unable to do before receiving AVR-RD-04 and that the protein is
potentially preventing the toxic accumulation of cystine crystals. Images of the patient s cornea also showed a substantial decline in corneal crystals. His eGFR has been stabilizing post-infusion, though it is important to note that he had pre-existing, irreversible chronic kidney disease prior to trial enrollment. VCN has reached its therapeutic plateau, as expected, measuring 0.9 vcn/dg at 12-months
post-dosing, mirroring trends seen in AVROBIO s other clinical programs. Patient 2 had a VCN of 2.2 vcn/dg at three months post-gene therapy, as of Oct. 13, 2020. A new patient has been dosed this month in the investigator-sponsored1 study of AVR-RD-04 for cystinosis, marking the halfway point for enrollment with three patients dosed in total.
No unexpected safety events or trends have been identified in the trial, with no serious
adverse events reported as of the Nov. 2, 2020, safety data cut-off date.
Pioneering approach to personalized
conditioning to leverage advantages of busulfan
The company also shared new data on the safety and tolerability profile of precision conditioning with
busulfan prior to gene therapy administration. AVROBIO is pioneering a new approach called targeted concentration intervention (TCI) that enables precise dosing designed to optimize engraftment durability and head-to-toe reach of ex vivo lentiviral gene therapies. TCI aims to maximize the likelihood of engraftment while minimizing the risk of
out-of-range side effects by targeting busulfan exposure to an area under the curve of 90 mg x hr/L over four days, called
In AVROBIO s clinical trials to date, data suggest that side effects from its single-agent,
single-cycle approach to Bu90-TCI conditioning may be predictable, manageable and transient. The side effects have tended to be mild to moderate in nature and typically presented one week after dosing and peak
over three to four days before quickly subsiding. Unlike other conditioning agents, Bu90-TCI is lymphocyte sparing, meaning that important components of the adaptive immune system, B and T cells, are expected
to be minimally affected.
Strategic pipeline expansion into relentlessly progressive lysosomal disorders
AVROBIO announced the addition of Gaucher disease type 3 to its pipeline, following the recent addition of Hunter syndrome, which is planned to enter the
clinic next year. Together with the existing program in Pompe disease, these make up AVROBIO s second wave of clinical programs focused on life-threatening lysosomal disorders, with the goals of preventing the central nervous system and
systemic deterioration that make lysosomal disorders so devastating, normalizing lifespan and lifting the burden of chronic treatment with ERT. New preclinical data suggest that AVROBIO s proprietary tagging technology, part of its
industry-leading plato gene therapy platform toolbox, further enhances the potential of its investigational gene therapies in these disorders.
We believe that all six of our pipeline programs share tremendous synergies in clinical development,
manufacturing, regulatory processes and commercialization. This second wave of programs will evaluate our promising investigational therapies in diseases with high unmet medical need for patients and families, said Chris Mason, M.D., Ph.D.,
chief scientific officer at AVROBIO. We believe the opportunity we have to potentially prevent patients, especially children, from developing the disabilities that would otherwise result from their inherited genetic code to perhaps give
them the possibility of a full and healthy life is humbling. That is our purpose; it drives all of us at AVROBIO every day.
The presented data showed that a lentiviral gene
therapy incorporating an ApoE2 tag used in AVR-RD-05 and in-licensed from the University of Manchester, U.K., substantially
reduced substrate accumulation and neuroinflammation in mouse models of Hunter syndrome to levels seen in normal mice. The presence of the tag significantly improved performance across multiple metrics in preclinical models, including normalization
of skeletal features such as the cheekbone dimensions and the width of the humerus and femur bones. Patient dosing is planned to begin in 2H 2021 in an investigator-sponsored trial with the University of Manchester. The company is exploring
regulatory options, including expedited development programs, to advance the product for use in neuronopathic patients, the most severe form of the disease.
The disease burden for patients with Gaucher disease type 3 includes significant neurological deterioration, which AVROBIO believes AVR-RD-06 has the potential to address by replacing diseased microglia and macrophages, or Gaucher cells, with genetically modified cells throughout the body and
The presented data showed that a lentiviral gene therapy incorporating a proprietary Glycosylation-Independent Lysosomal Targeting (GILT)
tag used in AVR-RD-03 and in-licensed from BioMarin, reduced toxic glycogen accumulation by 97 to 100 percent in tissues
including the brain, spinal cord, heart and diaphragm, and by more than 85 percent in skeletal muscle in a mouse model of the most severe form of the disease, classic infantile-onset Pompe disease. Four to eight months after dosing, substrate
levels in multiple tissues of the mice treated with the tagged lentiviral gene therapy were nearly indistinguishable from normal mice. AVROBIO believes that these exciting results could only be achieved with the GILT tag to drive uptake into hard-to-reach tissues. The company is exploring options to rapidly advance AVR-RD-03 into the
clinic for treatment of classic infantile-onset Pompe disease.
platform ready to enable global commercialization
AVROBIO also presented data on its industry-leading plato platform highlighting advances in chemistry, manufacturing and controls (CMC) to prepare for planned upcoming trials and potential global commercialization.
The optimized processes embedded in plato are designed to enable robust product characterization and efficient production of potent, consistent drug product
on two continents, with a third site slated to become operational in Europe in 2021. New advances include:
R&D Day webcast information
Virtual R&D Day and accompanying slides will be available under Events and Presentations in the Investors section of the company s website at www.avrobio.com. An archived webcast recording of the event will be available
on the website for approximately 30 days.
Our vision is to bring personalized gene therapy to the world. We aim to prevent, halt or reverse disease throughout the body with a single dose of gene
therapy designed to drive durable expression of functional protein, even in hard-to-reach tissues and organs including the brain, muscle and bone. Our ex vivo lentiviral
gene therapy pipeline includes clinical programs in Fabry disease, Gaucher disease type 1 and cystinosis, as well as preclinical programs in Hunter syndrome, Gaucher disease type 3 and Pompe disease. AVROBIO is powered by its industry
leading plato gene therapy platform, our foundation designed to deliver gene therapy worldwide. We are headquartered in Cambridge, Mass., with an office in Toronto, Ontario. For
Forward-Looking Statement
This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities
Litigation Reform Act of 1995. These statements may be identified by words and phrases such as aims, anticipates, believes, could, designed to, estimates, expects,
forecasts, goal, intends, may, plans, possible, potential, seeks, will, and variations of these words and phrases or similar expressions that
are intended to identify forward-looking statements. These forward-looking statements include, without limitation, statements regarding our business strategy for and the potential therapeutic benefits of our prospective product candidates, results
of preclinical studies, the design, commencement, enrollment and timing of ongoing or planned clinical trials, clinical trial results, product approvals and regulatory pathways, anticipated benefits of our gene therapy platform including potential
impact on our commercialization activities, timing and likelihood of success, and the expected benefits and results of our implementation of the plato platform in our clinical trials and gene therapy programs, including the use of a personalized and
ultra-precision busulfan conditioning regimen. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. Results in preclinical or early-stage clinical trials may not be